Treatment of bacterial infections

Details Treatment of bacterial infections Treatment of bacterial infections

C - Chemistry, Metallurgy

07

H

C07H 15/04 (2006.01) A61K 31/70 (2006.01) A61K 31/7016 (2006.01) A61K 31/702 (2006.01) A61P 31/04 (2006.01) C07H 1/00 (2006.01) C07H 15/00 (2006.01) G01N 33/53 (2006.01) G01N 33/569 (2006.01)

Patent

CA 2339198

Compounds which bind to toxins associated with enteric bacterial infection, compositions including the compounds, methods for the neutralization of toxins in a patient, and methods for the diagnosis of bacterial and viral infections are disclosed. Toxins which can be bound by the compounds include pentameric toxins, for example SLTs, such as those from salmonella, camylobacter and other bacteria, verotoxins from E. coli, cholera toxin, clostridium difficile toxins A and B, bacterial pili from enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) and viral lectins such as viral hemagglutinins. The compounds include a core molecule bound to a plurality of linker arms, which in turn are bound to a plurality of bridging moieties, which in turn are bound to at least one, and preferably, two or more ligands which bind to the toxin. Examples of suitable ligands include di- and for trisaccharide moieties. The di- or tri-saccharide moieties themselves are active in binding to the SLTs. The presence of a plurality of briged dimers of the ligands is responsible for the increased binding affinity of the compounds relative to the ligands themselves. In one embodiment, the compounds, when administered in a timely fashion to a patient suffering from enteric E. coli infection, inhibit progression of this infection into hemolytic uremic syndrome (HUS).

L'invention porte: sur des composés se fixant à des toxines associées à des infections à entérobactéries, sur des compositions comprenant ces composés; sur des procédés de neutralisation de toxines chez un patient, et sur des méthodes de diagnostic des infections bactériennes et virales. Les toxines auxquelles se fixent les composés comprennent des toxines pentamères telles que les SLT, par exemple celles de la salmonella, du camylobacter et d'autres bactéries, les vérotoxines du E. coli, les toxines du choléra, les toxines des clostridium difficile A et B, le pili bactérien du E. colientéropathogénique (EPEC) et du E. coli entérotoxigénique (ETEC) ainsi que des lectines virales telles que les hémagglutinines virales. Ces composés comportent une molécule noyau liée à plusieurs bras de liaison, à leur tour liés à plusieurs fragments de pontage, à leur tour liés à un ou de préférence plusieurs ligands qui se fixent à la toxine. Parmi les ligands idoines se trouvent des fragments de di et trisaccharides se fixant eux-mêmes aux SLT. La présence des différents dimères pontés des ligands est responsable de l'affinité accrue de liaison des composés vis-à-vis des ligands eux-mêmes. Dans l'une des exécutions, les composés administrée à temps à un patient souffrant d'une infection à E. Coli, l'empêchent de dégénérer en syndrome de Gasser.

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